1. Field of the Invention
The present invention relates to a method for treating muscular dystrophy.
2. Description of the Related Art
Main pathological changes by muscular dystrophy are degeneration and necrosis of skeletal muscle. Clinically, muscular dystrophy is a genetic disease accompanied with progressive loss of muscle strength.
As causes of muscular atrophy leading to a loss of muscle strength, an abnormality of in motor nerves in addition to an abnormality of muscle itself is exemplified. A muscular atrophy due to an abnormality of muscle itself is called as myogenic muscular atrophy, and a muscular atrophy due to an abnormality of motor nerves is called as neurogenic muscular atrophy. In neurogenic muscular atrophy, no abnormality is found in muscle but an abnormality appears in motor nerves and muscles movement, leading to muscular atrophy. Muscular dystrophy is a representative disease of myogenic muscular atrophy.
Although the cause of muscular dystrophy is not quite clear, deficiencies and abnormalities in a series of proteins of dystrophin present just below a muscular plasma membrane, adhalin present in a plasma membrane, merosin present in a basement membrane and the like are considered as possible causes.
Based on such knowledge, it is considered as a possible treatment for muscular dystrophy to induce dystrophin and the like. However, their effectiveness has not been confirmed in clinical trials.
As a therapeutic drug, a protein anabolic hormone, a growth hormone, a calcium antagonist, a protein-degrading enzyme inhibitor such as bestatin, a muscle relaxant such as sodium dantrolene and the like have been used so far. However, although these drugs exhibit a certain degree of inhibiting effect on progression of symptoms at an initial period of administration, the effect does not last. Thus, in the present situation, rehabilitation and the like are mainly carried out as a treatment for preventing progression of dysfunction. Namely, the drugs having a sufficient therapeutic effect on muscular dystrophy have not been known. Therefore, drugs for treating muscular dystrophy have been studied.
For example, it is described in TAKAOKA et al., Journal of Bone and Mineral Metabolism, vol. 18, pp. 2-8 (2000), that a patient of progressive muscular dystrophy who had almost been immobilized for 4 years was administered a crude extract derived from pig pancreas. As a result, an improvement was seen in one week, and the patient could go back home in one month. It is further described in the document that a muscular dystrophy patient was administered the same crude extract, so that the patient gained weight in 8 months and came to be able to raise the leg high in 10 months.
However, precise experimental conditions are not described in the above academic document at all, so the reliability of the results is questionable. For example, it is unlikely that no other treatment was taken at all while the crude extract was administered; therefore, there is no certain evidence that the above improvement effects are resulted from the crude extract alone. In fact, although it is described in the document that the above crude extract has a strong activity for reducing BUN, i.e. serum urea nitrogen level, which is to be an indicator of muscular dystrophy, the effect was weak when the present inventors carried out a similar experiment.
In the above academic document, it is also described that N-terminal amino acid sequence of the protein further purified from the crude extract indicates high homology with human elastase IIIB. In addition, it is concluded that bone/calcium metabolism regulating activity of the crude extract results from elastase IIIB.
However, the effects of human elastase IIIB on muscular dystrophy have not been proved directly, and there is no report of its clinical use. Of course, it has not been put to practical use.
Tomomura who is one of the inventors of the present invention isolated caldecrin from pig pancreas and found that the caldecrin reduces serum calcium level (Japanese unexamined patent publication No. 4-279598). Further, Tomomura completed method of producing caldecrin using a caldecrin gene (Japanese unexamined patent publication No. 8-298990). However, the effects of the caldecrin on muscular dystrophy have never reported so far.